Project description:Expression profiling of nasopharyngeal carcinoma patients comparing radio-sensitive samples with radio-resistant samples. Two condition-experiments, radio-sensitive and radio-resistant nasopharyngeal carcinoma patients. Biological replicates: 8 radio-sensitive, 12 radio-resistant, different donors in the same hospital. One patient per array.
Project description:We established panels of patient-derived culture of the cancer cells from small cell carcinoma of the cervix uteri (SCCC) by cancer tissue–originated spheroids (CTOS) method. Then we developed in vitro sensitivity assay for radiation using CTOSs to assess the intrinsic radio-sensitivity and mechanism of radio-resistance in individual SCCC patients. To find factors that affect to the radio-sensitivity we compared gene expression of radio-resistant CTOS (cerv-5) and radio-sensitive CTOS (cerv-9).
Project description:We established panels of patient-derived culture of the cancer cells from small cell carcinoma of the cervix uteri (SCCC) by cancer tissueM-bM-^@M-^Soriginated spheroids (CTOS) method. Then we developed in vitro sensitivity assay for radiation using CTOSs to assess the intrinsic radio-sensitivity and mechanism of radio-resistance in individual SCCC patients. To find factors that affect to the radio-sensitivity we compared gene expression of radio-resistant CTOS (cerv-5) and radio-sensitive CTOS (cerv-9). We compared gene expression of cerv5 and cerv9 CTOSs under the culture condition.
Project description:Chimeric antigen receptor (CAR) T-cell therapy has limited efficacy against solid tumors such as neuroblastoma (NB). Key obstacles include extensive tumor burden and the presence of an immunosuppressive tumor microenvironment (TME). We employ targeted radiopharmaceutical therapy (RPT) using [67Cu]Cu-LLP2A and find that it potentiated the anti-tumor activity of CAR T-cells in radio-sensitive and radio-resistant NB models via distinct mechanisms. In radio-sensitive NB, RPT is directly tumoricidal while also enhancing CAR T-cell efficacy through pro-immune pathways, most notably via the TNFα pathway, leading to paracrine activation of T-cells. In radio-resistant NB, RPT improves CAR T-cells by remodeling the myeloid compartment in the TME and increasing the formation of immunological niches of cytotoxic CD8⁺ GZMB⁺ and CD4⁺ GZMB+ CAR T-cells. While neither treatment modality alone can effectively treat NB, the combination of VLA-4-targeted RPT and GD2 or B7-H3 CAR T-cells augments anti-tumor efficacy, resulting in marked tumor regression in preclinical NB models.
Project description:Chimeric antigen receptor (CAR) T-cell therapy has limited efficacy against solid tumors such as neuroblastoma (NB). Key obstacles include extensive tumor burden and the presence of an immunosuppressive tumor microenvironment (TME). We employ targeted radiopharmaceutical therapy (RPT) using [67Cu]Cu-LLP2A and find that it potentiated the anti-tumor activity of CAR T-cells in radio-sensitive and radio-resistant NB models via distinct mechanisms. In radio-sensitive NB, RPT is directly tumoricidal while also enhancing CAR T-cell efficacy through pro-immune pathways, most notably via the TNFα pathway, leading to paracrine activation of T-cells. In radio-resistant NB, RPT improves CAR T-cells by remodeling the myeloid compartment in the TME and increasing the formation of immunological niches of cytotoxic CD8⁺ GZMB⁺ and CD4⁺ GZMB+ CAR T-cells. While neither treatment modality alone can effectively treat NB, the combination of VLA-4-targeted RPT and GD2 or B7-H3 CAR T-cells augments anti-tumor efficacy, resulting in marked tumor regression in preclinical NB models.
Project description:During radiotherapy most cancer cells are removed, but some cells are not. These remained cancer cells become resistant to radiotherapy and lead to cancer recurrence. Radioresistnat cancer cells show different gene expression profile than radiosensitive tumor cells. Among the genes distinctly up or down-changed in expression level, some are associated with development of radioresistance. We used microarrays to select multiple genes showing distinct change in expression level for seeking genes that contribute to the develpoment of radioresistance in breast cancer cells during radiotherapy.
Project description:Human breast cancer cell line MCF-7 is usually sensitive to chemotherapy drug BMS-554417, an insulin receptor (IR) and insulin-like growth factor receptor (IGFR) inhibitor. However, through step-wise increase in BMS-554417 doses in culture media, we were able able to screen and select a single MCF-7 clone that is BMS-554417 resistant. It is cross resistant to BMS-536924. This new line of MCF-7 cells was named as MCF-7R4. The transcriptome profiling of both MCF-7 and MCF-7R4 was performed using Affymetrix HG-U133 plus2.0 GeneChip arrays.